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In the isolated perfused heart phenylephrine‐induced activation of ERK is attenuated by glucosamine
Author(s) -
Zhu Xiaoyuan,
Marchase Richard B,
Chatham John C
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.970.47
Subject(s) - phosphorylation , mapk/erk pathway , chemistry , phenylephrine , glucosamine , p38 mitogen activated protein kinases , medicine , endocrinology , protein kinase b , pharmacology , biochemistry , blood pressure
We have shown that in the heart increased hexosamine biosynthesis pathway (HBP) flux inhibits phenylephrine (PE)‐induced inotropy; however, the mechanisms underlying this are unclear. Therefore, the goal of this study was to determine the effect of increased HBP flux on α‐adrenergic signaling pathways in the heart. Isolated rat hearts were perfused with or without 5mM glucosamine (GlcN) and were treated with or without 10μM PE for 15 mins and p38, Akt and ERK phosphorylation assessed by immunoblot. PE increased rate‐pressure product ~2‐fold and this was significantly attenuated with GlcN (p<0.05). There was no effect of either PE or GlcN on p38 phosphorylation and although PE increased p‐Akt ~2‐fold (p<0.05) this was unaffected by GlcN. However, in the absence of GlcN, PE increased ERK phosphorylation 6.5‐fold (p<0.05), but only ~2‐fold with GlcN (p<0.05 vs. no GlcN). Surprisingly, basal ERK phosphorylation by was increased 2.4‐fold by GlcN (p<0.05 vs. no GlcN); however, even correcting for this ERK phosphorylation was still significantly lower with GlcN + PE compared to PE with no GlcN (4.8±0.4 vs. 6.5±0.4; p<0.05). These data demonstrate that increasing HBP flux with GlcN alters PE‐induced activation of ERK but not p38 or Akt. Further studies are needed to determine if this contributes to the blunted inotropic response to PE.